Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit

Cascio, Giuliana Lo; Koncan, Raffaella; Stringari, G.; Russo, Alessandro; Azzini, Anna Maria; Ugolini, Alessio; Ligozzi, Marco; Polati, Enrico; Cornaglia, Giuseppe; Concia, Ercole; Schweiger, Vittorio

doi:10.1007/s10096-014-2239-z

Cited by 24 publications

(11 citation statements)

References 34 publications

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“…This will hopefully be associated with the following most appreciated side effects: (1) primary cost savings (e.g., due to the waiving of expensive antifungal drugs and reduced hospital and ICU stay) and (2) reducing drug resistance rates (with secondary cost savings). Although the combined use of BDG and PCT was recently described to be suitable for early differential diagnosis between candidemia and bacteremia in intensive care units [22], the diagnostic value of BDG for IFI diagnosis is not free of doubts and subject of controversial discussions [37][38][39][40]. In line with that, BDG recently failed to be a suitable biomarker for reliable IFI diagnosis in septic shock within the presented cohort [21].…”

Section: Discussionmentioning

confidence: 98%

Soluble Intercellular Adhesion Molecule- (sICAM-) 1, Thrombospondin-1, and Vinculin for the Identification of Septic Shock Patients Suffering from an Invasive Fungal Infection

Decker

Incamps²,

Sigl

et al. 2020

Mediators of Inflammation

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Background. Nowadays, invasive fungal infections (IFI) are of increasing importance and associated with an increased mortality. However, reliable diagnostic tools for the identification of patients suffering from an IFI are rare and associated with relevant weaknesses. Methods. Within this secondary analysis of an observational clinical study, an innovative biomarker panel (consisting of 62 biomarkers in total) was screened for the identification of septic shock patients suffering from an IFI. Fungal growth in blood cultures, intraoperative swabs, and Aspergillus spp. in deep respiratory tract specimens with accompanying pulmonary infiltrates were classified as infection, whereas Candida spp. in the respiratory tract or in fluids from drainages were classified as colonization. Plasma samples of 50 septic shock patients at six predefined timepoints within a period of 28 days following the onset of septic shock were available. Results. In total, 11 out of the 50 patients (22%) were shown to suffer from an IFI, whereas 22 patients (44%) presented with a fungal colonization. Within the presented biomarker panel, plasma levels of soluble intercellular adhesion molecule-(sICAM-) 1, thrombospondin-1, and vinculin were shown to be the most promising. sICAM-1 was shown to be increased in patients with an IFI, whereas thrombospondin-1 and vinculin revealed decreased plasma levels as compared to colonized patients as well as patients without any fungal findings at any time. Conclusion. Plasmatic measurements of sICAM-1, thrombospondin-1, and vinculin may help to facilitate the diagnosis of an IFI in human septic shock and to identify patients with an increased risk for an IFI. This trial is registered with DRKS00005463.

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Section: Discussionmentioning

confidence: 98%

Soluble Intercellular Adhesion Molecule- (sICAM-) 1, Thrombospondin-1, and Vinculin for the Identification of Septic Shock Patients Suffering from an Invasive Fungal Infection

Decker

Incamps²,

Sigl

et al. 2020

Mediators of Inflammation

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“…Elevated BDG serum concentrations of more than 80 pg/ml have a high diagnostic accuracy to predict ICI [12, 13, 18, 33, 34]. However, the available data suggest that many ICU interventions may interfere by increasing BDG serum concentrations [11, 14, 15]. In addition, the diagnostic accuracy of BDG has been reported only for candidemia rather than ICI in general and may also depend on the fungal species [12].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, falsely increased BDG serum concentrations in the absence of ICI may be induced by several common ICU interventions. For example, concurrent bacteremia, hemodialysis membranes, administrations of blood products, and treatment with albumin or immunoglobulin products can interfere with BDG measurements [11, 14, 15]. If relevant, this type of interference would significantly reduce the clinical usability of BDG assays in critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

(1,3)-β-D-glucan-based diagnosis of invasive Candida infection versus culture-based diagnosis in patients with sepsis and with an increased risk of invasive Candida infection (CandiSep): study protocol for a randomized controlled trial

Bloos

Held

Brillinger

et al. 2018

Trials

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BackgroundThe time to diagnosis of invasive Candida infection (ICI) is often too long to initiate timely antifungal therapy in patients with sepsis. Elevated serum (1,3)-β-D-glucan (BDG) concentrations have a high diagnostic sensitivity for detecting ICI. However, the clinical significance of elevated BDG concentrations is unclear in critically ill patients. The goal of this study is to investigate whether measurement of BDG in patients with sepsis and a high risk for ICI can be used to decrease the time to empiric antifungal therapy and thus, increase survival.Methods/designThis prospective multicenter open randomized controlled trial is being conducted in 19 German intensive care units. All adult patients with severe sepsis or septic shock and an increased risk for ICI are eligible for enrolment. Risk factors are total parenteral nutrition, previous abdominal surgery, previous antimicrobial therapy, and renal replacement therapy. Patients with proven ICI or those already treated with systemic antifungal substances are excluded. Patients are allocated to a BDG or standard care group. The standard care group receives targeted antifungal therapy as necessary. In the BDG group, BDG serum samples are taken after randomization and 24 h later. Antifungal therapy is initiated if BDG is ≥80 pg/ml in at least one sample. We plan to enroll 312 patients. The primary outcome is 28-day mortality. Other outcomes include antifungal-free survival within 28 days after enrolment, time to antifungal therapy, and the diagnostic performance of BDG compared to other laboratory tests for early ICI diagnosis. The statistical analysis will be performed according to the intent-to-treat principle.DiscussionBecause of the high risk of death, American guidelines recommend empiric antifungal therapy in sepsis patients with a high risk of ICI despite the limited evidence for such a recommendation. In contrast, empiric antifungal therapy is not recommended by European guidelines. BDG may offer a way out of this dilemma since BDG potentially identifies patients in need of early antifungals. However, the evidence for such an approach is inconclusive. This clinical study will generate solid evidence for health-care providers and authors of guidelines for the use of BDG in critically ill patients.Trial registrationClinicaltrials.gov, NCT02734550. Registered 12 April 2016.

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“…In IVIg products containing maltose, erroneously elevated blood sugar values can occur when using GDH-PQQ test strips [87]. Diagnostic assays using Beta-D-Glucan for fungal testing can be false positive [88]. Immunoglobulin treatment can transfer antibodies to blood groups, affecting serological test.…”

Section: Miscellaneousmentioning

confidence: 99%

Treatment and management of primary antibody deficiency: German interdisciplinary evidence‐based consensus guideline

et al. 2020

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This evidence‐based clinical guideline provides consensus‐recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. Recommendations were based on results of a systematic literature search, data extraction, and evaluation of methodology and study quality in combination with the clinical expertise of the respective representatives. Consensus‐based recommendations were determined via nominal group technique. PADs are the largest clinically relevant group of primary immunodeficiencies. Most patients with PADs present with increased susceptibility to infections, however immune dysregulation, autoimmunity, and cancer affect a significant number of patients and may precede infections. This guideline therefore covers interdisciplinary clinical and therapeutic aspects of infectious (e.g., antibiotic prophylaxis, management of bronchiectasis) and non‐infectious manifestations (e.g., management of granulomatous disease, immune cytopenia). PADs are grouped into disease entities with definitive, probable, possible, or unlikely benefit of IgG‐replacement therapy. Summary and consensus‐recommendations are provided for treatment indication, dosing, routes of administration, and adverse events of IgG‐replacement therapy. Special aspects of concomitant impaired T‐cell function are highlighted as well as clinical data on selected monogenetic inborn errors of immunity formerly classified into PADs (APDS, CTLA‐4‐, and LRBA‐deficiency).

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Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit

Cited by 24 publications

References 34 publications

Soluble Intercellular Adhesion Molecule- (sICAM-) 1, Thrombospondin-1, and Vinculin for the Identification of Septic Shock Patients Suffering from an Invasive Fungal Infection

Soluble Intercellular Adhesion Molecule- (sICAM-) 1, Thrombospondin-1, and Vinculin for the Identification of Septic Shock Patients Suffering from an Invasive Fungal Infection

(1,3)-β-D-glucan-based diagnosis of invasive Candida infection versus culture-based diagnosis in patients with sepsis and with an increased risk of invasive Candida infection (CandiSep): study protocol for a randomized controlled trial

Treatment and management of primary antibody deficiency: German interdisciplinary evidence‐based consensus guideline

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